Preliminary data indicate that metabolism of the polychlorinated biphenyls and dioxins is necessary if maximum toxicity is to be experienced in animals. Experiments are in progress utilizing H3-2,2,5,5-tetrachlorobiphenyl (PCB) and C14 tetrachlorodibenzo-rho-dioxin (TCDD) to determine their degree of absorption, tissue deposition, and rate of excretion in rats and nonhuman primates. In these experiments animals will be killed at definite intervals in order to determine the movement of TCDD or PCB through the body. Feces and urine will be collected to monitor the rate of elimination of the radioactive material from the body. Major metabolites of these compounds will be isolated by thin-layer chromatography and gas chromatography. Purified metabolites will be identified by ultraviolet, infrared, and nuclear magnetic resonance spectroscopy, mass spectrometry, and C.H.N. analysis. The major metabolites will subsequently be confirmed by synthesis and administered to experimental animals to determine toxicity. During the course of the above mentioned experiments additional animals will be placed on compounds such as phenobarbital which is known to enhance the activity of hepatic microsomal enzymes and SKF-525A, an inhibitor of microsomal enzyme activity. This will be followed by the administration of the PCBs or dioxins. Modification in the toxic effects of these compounds by altering the microsomal enzyme activity will also be helpful in determining the relationship of metabolism of these compounds to toxicity.